Department of Entomology, University of Maryland, College Park, Maryland, United States of America.
PLoS One. 2011;6(11):e26796. doi: 10.1371/journal.pone.0026796. Epub 2011 Nov 2.
Honey bees (Apis mellifera) have recently experienced higher than normal overwintering colony losses. Many factors have been evoked to explain the losses, among which are the presence of residues of pesticides and veterinary products in hives. Multiple residues are present at the same time, though most often in low concentrations so that no single product has yet been associated with losses. Involvement of a combination of residues to losses may however not be excluded. To understand the impact of an exposure to combined residues on honey bees, we propose a mechanism-based strategy, focusing here on Multi-Drug Resistance (MDR) transporters as mediators of those interactions.
METHODOLOGY/PRINCIPAL FINDINGS: Using whole-animal bioassays, we demonstrate through inhibition by verapamil that the widely used organophosphate and pyrethroid acaricides coumaphos and τ-fluvalinate, and three neonicotinoid insecticides: imidacloprid, acetamiprid and thiacloprid are substrates of one or more MDR transporters. Among the candidate inhibitors of honey bee MDR transporters is the in-hive antibiotic oxytetracycline. Bees prefed oxytetracycline were significantly sensitized to the acaricides coumaphos and τ-fluvalinate, suggesting that the antibiotic may interfere with the normal excretion or metabolism of these pesticides.
CONCLUSIONS/SIGNIFICANCE: Many bee hives receive regular treatments of oxytetracycline and acaricides for prevention and treatment of disease and parasites. Our results suggest that seasonal co-application of these medicines to bee hives could increase the adverse effects of these and perhaps other pesticides. Our results also demonstrate the utility of a mechanism-based strategy. By identifying pesticides and apicultural medicines that are substrates and inhibitors of xenobiotic transporters we prioritize the testing of those chemical combinations most likely to result in adverse interactions.
近年来，蜜蜂（Apis mellifera）的越冬蜂群死亡率高于正常水平。有许多因素被认为可以解释这种损失，其中包括蜂箱中农药和兽药残留的存在。尽管大多数情况下浓度较低，但同时存在多种残留，因此尚未将单一产品与损失联系起来。然而，不能排除多种残留共同作用导致损失的可能性。为了了解接触混合残留对蜜蜂的影响，我们提出了一种基于机制的策略，这里重点关注多药耐药（MDR）转运蛋白作为这些相互作用的介质。
方法/主要发现： 通过使用全动物生物测定法，我们通过维拉帕米的抑制作用证明了广泛使用的有机磷和拟除虫菊酯杀螨剂氯菊酯和τ-氟氯氰菊酯，以及三种新烟碱类杀虫剂：吡虫啉、噻虫胺和噻虫嗪，都是一种或多种 MDR 转运蛋白的底物。在蜜蜂 MDR 转运蛋白的候选抑制剂中，有一种是在蜂箱中使用的抗生素土霉素。预先喂食土霉素的蜜蜂对杀螨剂氯菊酯和τ-氟氯氰菊酯的敏感性显著增加，这表明抗生素可能干扰这些杀虫剂的正常排泄或代谢。
结论/意义： 许多蜂箱经常接受土霉素和杀螨剂的治疗，以预防和治疗疾病和寄生虫。我们的结果表明，这些药物在季节性联合应用于蜂箱时，可能会增加这些和其他农药的不良影响。我们的结果还证明了基于机制的策略的有效性。通过识别作为外源性转运蛋白底物和抑制剂的农药和养蜂药物，我们优先测试那些最有可能导致不良相互作用的化学组合。
